Throughout this application various publications are referred to in parenthesis. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications are hereby incorporated by reference in their entireties into the subject application to more fully describe the art to which the subject application pertains.
Melanin is a high molecular weight pigment that is ubiquitous in nature and has a variety of biological functions (1). Melanins are found in all biological kingdoms. These pigments are among the most stable, insoluble, and resistant of biological materials (30). Melanins can have different structures depending on the biosynthetic pathway and precursor molecules. Some definitions of melanin have focused on chemical and physical properties of melanins instead of defined structures (29). Melanins can be synthesized in the laboratory by chemical means or by many living organisms. Melanins formed by the oxidative polymerization of phenolic compounds are usually dark brown or black (30). However, melanins may have other colors as illustrated by the finding that dopamine-derived melanin is reddish-brown. Fungi can make melanins from at least two major biosynthetic pathways, employing the precursor 1,8-dihydroxynapthalene (DHN melanin) or the oxidation of suitable tyrosine derivatives like dihydroxyphenylalanine (DOPA-melanin) (30). The fungus C. neoformans can make melanins from a wide variety of phenolic compounds which are oxidized by a laccase enzyme (31-33).
Melanins protect against UV light by absorbing a broad range of the electromagnetic radiation (1), and the melanin pigment is used in photo-protective creams (10). The presence of melanin is implicated in the resistance of human malignant pigmented melanoma to radiation therapy (9). Many fungi constitutively synthesize melanin (2). The ability of free-living microorganisms to make melanin may be associated with a survival advantage in the environment (3) that includes protection against solar radiation (reviewed in 4). Melanized fungi are also resistant to ionizing radiation (5). An example of such radiation resistance is provided by reports that melanized fungi colonize the walls of the damaged nuclear reactor in Chernobyl (6). The soils around the damaged reactor have blackened as the resident flora changes to include disproportionately more melanotic fungi (7). Water in nuclear reactor cooling pools is sometimes contaminated with melanized microorganisms (8). However, despite the finding of melanotic organisms in such harsh environments, the contribution of melanin to the radiation resistance of these organisms is uncertain.